Hemminki K, Kallama S
IARC Sci Publ. 1986(78):55-70.
This paper summarizes the mechanism of action and the covalent modifications of nucleic acids, nucleotides and nucleosides by nitrogen mustards. Nitrogen mustards react preferentially with guanine N7 in DNA in vitro. A few minor adducts have been characterized. Cross-links of nitrogen mustard and metabolites of cyclophosphamide that have been identified are diguanyl derivatives linked at N7. It is essential that studies of alkylation products in vivo be carried out, since characterization of alkylation products of cytostatic drugs should provide further insight into the mechanisms of cytotoxicity and, consequently, facilitate the development of more efficient anticancer agents. Furthermore, the monitoring of DNA adducts of therapeutic significance in patients may provide new avenues for the individualization of cancer therapy.
本文总结了氮芥对核酸、核苷酸和核苷的作用机制及共价修饰。体外实验中，氮芥优先与DNA中的鸟嘌呤N7发生反应。已鉴定出一些少量的加合物。已确定的氮芥和环磷酰胺代谢物的交联物是在N7处相连的双鸟嘌呤衍生物。对体内烷基化产物进行研究至关重要，因为对细胞抑制药物烷基化产物的表征应能进一步深入了解细胞毒性机制，从而有助于开发更有效的抗癌药物。此外，监测患者体内具有治疗意义的DNA加合物可能为癌症治疗的个体化提供新途径。
